Certain bone and connective tissue disease processes are detectable by monitoring the level of certain macromolecules in the serum. An example is serum osteocalcin, the levels of which reflect bone turnover. However, heretofore, only a limited number of such macromolecules were known to be related to bone and connective tissue diseases. The macromolecules cited herein comprise the majority (70% of the noncollagenous proteins in the human skeleton) that are truly of bone cell origin, that is the cDNA sequences were derived from screening of normal human bone cell cDNA libraries, and not from cDNA libraries of cells or tissues of other non-bone types, or of transformed cells. The levels in tissues or bodily fluids, such as serum, plasma, crevicular fluid, amniot fluid, urine, etc., of these molecules or their metabolites reflect normal bone metabolism. A shift in those levels from the normal values would be indicative of skeletal and/or connective tissue disease states.